Sloan-Ketterings' Dr. Peter Bach wrote a column (CT Scam: Don't believe the hype about lung-cacer screenings") in Slate on the evidence, the harms, the costs and the marketing that has exploded all over the country after this National Lung Screening Trial results were published.

November is Lung Cancer Awareness month. In Atlanta this week you may have heard a dulcet-voiced doctor on the radio announcing that "anybody can develop lung cancer," and the alarming factoid that women who have never smoked are the fastest-growing segment of people getting the diagnosis. In California, a press release announced that anyone who has smoked for more than 10 years is a "patient at risk" for lung cancer, and another advised that "prior smokers over 50 years of age "would benefit from screening.

But these are not public-service announcements intended to raise awareness of the No. 1 cancer-killer. They are advertisements promoting computed tomography lung cancer screening from St. Joseph's Hospital in Atlanta, Wilshire Radiology Associates in Beverly Hills, Calif., and the Bonnie Addario Lung Cancer Foundation (which sponsors a CT screening program at Sequoia Hospital in Redwood City, Calif.). There are more examples, too—coming from hospital Web sites and physicians' groups. And they are all dangerously misleading.

On Nov. 4, the National Cancer Institute held a press conference announcing that a large randomized trial of CT screening had shown an astounding 20 percent reduction in the risk of death from lung cancer among participants. This is a huge step forward in lung-cancer prevention, no doubt. But the Institute said little about who should be screened, or the risks that are involved.

They should have. Cancer screening is fundamentally inefficient: Hundreds, and sometimes thousands, of people must be screened to help just one or two. Each person who undergoes the test may suffer consequences from it, even though most will never get any counterbalancing benefit. This is why the recent study—called the National Lung Screening Trial—focused on a narrow, "high-risk" subgroup of the adult population who ranged from 55 to 74 years old and had smoked at least a pack a day for 30 years. If they had quit, it was within the past 15 years.

These are strict criteria, and they ensured that the patients had a meaningful chance of developing lung cancer during the course of the decadelong study—and thus an opportunity to benefit from being screened. But people who are younger or have smoked less than the test subjects are at much lower risk for the disease (although no one is entirely safe from it).

If you have a lower risk of lung cancer, there's less of a chance that screening will help you, as you can't prevent something that wasn't going to happen. But that doesn't mean there's less of a chance you'll be harmed by the procedure. Taking a CT scan of the chest can uncover something that looks abnormal but ends up being nothing. Along the way there are more scans, biopsies and, sometimes, unnecessary surgeries. In the NCI study one in four people had these false positives. A prior study from the University of Pittsburgh pegged the rate at around two out of five, and in that study one in 100 subjects had parts of their lung removed for no good reason.

CT screening can also uncover small lung cancers that you'd be better off not knowing about, because they would be unlikely to progress and make you sick. This problem of overdiagnosis is familiar in prostate cancer—many cancers found by the PSA test are not dangerous. A study from 2007 showed that CT screening may uncover one overdiagnosed cancer for each real cancer it turns up. The NCI has not yet released the equivalent numbers from its new trial, but the data we do have suggest that the ratio is about the same—about one in 70 patients is told he has lung cancer when the condition might end up being harmless.

Leaving aside false positives and overdiagnoses, screening is not a panacea. Not even close. The NCI study showed that regular scans prevented one in five lung cancer deaths, which means that four out of five sneaked through. It's amazing to save even one in five people, but it also means that the number who benefit from screening is a lot smaller than the number who test positive. All told, a death from lung cancer was prevented in one out of every 300 people in the study.

The potential harms listed here are more than offset by this one important benefit. But that calculation changes if we stop focusing on those patients at very high risk of disease. For everyone else, the risks may outweigh the gains, and the overall cost in dollars would be prohibitive.

Insurance doesn't cover the test, and the NCI says that a scan costs about $300. But when I called about 50 places around the country, I heard numbers more like $1,800, with Sequoia Hospital in Redwood City topping the charts at $4,000. (Update, Nov. 29, 2010: The Bonnie Addario Foundation reports that a research study on lung cancer screening at Sequoia Hospital charges high-risk patients $399 out of pocket for the procedure.) To put this in perspective, there are about 7.5 million people in the United States at high risk of lung cancer like those the NCI studied. The price tag for screening all of them once would be at least $2 billion, and more like $13 billion if the prices I found are more accurate.

But the new round of CT scan advertisements released following the Nov. 4 press conference target a much larger population for screening. The Bonnie Addario Foundation's criteria suggest that some 46 million people should be screened at a cost of between $14 billion and $84 billion (about the budget of the U.S. Department of Education). Beverly Hills Radiologists? It says 77 million people and $23 billion to $138 billion (similar to the numbers for the Department of Labor). And if you go with St. Joseph's in Atlanta, which encourages screening for nonsmoking women and all men with any smoking exposure whatsoever, that's 166 million people—about half the U.S. population, at a cost of around $50 billion to $300 billion (half the Medicare program).

All of this would be for the first scan. Then there are the follow-up tests associated with false positives. If we stick to screening the high-risk people it will probably be worth it. Researchers at the Massachusetts General Hospital in Boston reported that it would cost around $150,000 for each quality-adjusted life year saved if we focused on screening those particular people. That's much more costly than, say, mammography, but it's in the neighborhood of many other cancer treatments. Still, these researchers noted that more could be gained at lower cost by getting people to stop smoking. Those who quit their habits reduce their risk of getting lung cancer by about 50 percent, which is more than double the benefit of being screened, without any of the radiation, false positives, overdiagnoses, and unnecessary surgeries.

Some day CT screening will save lives—hopefully a lot of them. It will harm some people, too. We can stay ahead in this tradeoff if we are circumspect about whom we screen, and if we don't believe every radio ad we hear.

Peter B. Bach is a pulmonary physician at Memorial Sloan-Kettering Cancer Center in New York City, where he directs the Center for Health Policy and Outcomes. He is a member of the Institute of Medicine's National Cancer Policy Forum and a board member of Fighting Chance.

"Long-awaited results from a big federal study show that screening smokers and former smokers with CT scans cuts the risk of dying from lung cancer by 20%. But many questions remain about how these findings should be applied to more than 90 million Americans who smoke or once did."

Researchers saw a 20% relative difference in lung cancer death rates. However, the absolute difference iin death rates was much less than two percent, because of the small number of few lung cancer deaths in either the spiral CT (354 or 1.32%) or x-ray (442 or 1.65%) group compared to the size of the total trial population (53,500).

Putting a spotlight on relative differences in rates usually magnifies the effects of an intervention. Absolute numbers - and the number of people that need to undergo the intervention in order for at least one to benefit - should get at least equal billing in order to put trial results into perspective.

Heavy smokers in this trial who were offered CT scans had a 20% lower rate of death from lung cancer than those offered chest x-rays (354 vs 442). But, because so many smokers were in this trial, the lung cancer death rate in each group was less than 2%. The absolute difference is 1.32% vs 1.65%).

The National Cancer Institute reported that 300 smokers would have to undergo screening in order for one life to be extended, at $300 to $1,000 a scan. And screening can lead to additional tests and treatments.

While CT scans are painless, they expose patients to radiation that can potentially cause new cancers. It is possible that a person scanned frequently for lung cancer could develop breast cancer as a result. The screening could lead to more potentially dangerous surgeries.

And screenings don't diagnose cancer. While screenings can detect potential problems, doctors need to retrieve actual cells to confirm cancer. Making an incision through the ribs to perform a lung biopsy is a serious operation and poses significant risks of its own.

The efficacy of screening for any medical condition depends not only upon test accuracy, but upon the efficacy of proceeding with definitive diagnosis and therapy versus the efficacy of doing nothing at all. There is no doubt that screening may identify cancer at an earlier stage than in the absence of screening.

Biologically, it appears that many cancers diagnosed at an earlier stage with screening are so aggressive that even at the time of earliest possible detection, there are already micrometastases, meaning that earlier extirpation of the primary tumor does not influence outcomes in a meaningful way.

More commonly, tumors are so indolent that metastases would not have occurred, even had diagnosis been delayed by one, two, or several years (i.e. until the lesion became palpable and was diagnosed in the former, pre-screening manner).

So the only patients helped by screening are those who are accurately detected by the screening exam and which have a "goldilocks" biology - not too aggressive, not too indolent. Balanced against this is the harm caused by screening, with respect to the false positives and the underlying morbidity of the screening procedure (e.g. radiation exposure).

I'm not being insensitive to the situation. I lost my brother-in-law (my wife's brother) to the overscreening and overtreatment process. He developed myelodysplastic syndrome (MDS) because of it. Sometimes with overscreening and overtreatment, while a life may be saved, a life may be taken. I have experienced for the second time in my life, the issue. It does happen, but no one emphasizes that point.

David Sampson, the American Cancer Society's director of medical and scientific communications, wrote on the ACS blog:

"It's only been a few days since researchers released preliminary results of a major trial of early detection of lung cancer in heavy smokers using CT scans. At the time, the American Cancer Society and others (including the authors themselves) expressed cautious optimism, with emphasis on the cautious, saying that although enormously promising, the data was not enough to call for routine use of this screening test, even in heavy smokers. But as we've discussed here, not everyone could resist the pull of touting the "good news" with little balance.

But our greatest fear was that forces with an economic interest in the test would sidestep the scientific process and use the release of the data to start promoting CT scans. Frankly, even we are surprised how quickly that has happened.

Last night, as he worked quietly in his home office, our Chief Medical Officer sat wide-eyed as he listened to an advertisement on an Atlanta radio station touting the results of the study to promote a local hospital's lung cancer screening program.

This morning, we were made aware of a press release from a group of doctors in Los Angeles promoting these scans. It actually appeared the day the news came out. It says:

"...this study should once and for all settle the controversy regarding the utility of screening CT of the lungs in saving lives."

As Dr. Len Lichtenfeld discussed in his blog, there is still much to discuss and learn about the test. And if you are someone who meets the criteria similar to people who participated in this study, then a scan might be worth considering. But before you do that, it would be wise to have a conversation with your health professional and consider whether screening is right for you. But oversimplifying these difficult issues in the pursuit of a compelling story or of paying clients is a disservice to public health.

We use changes in tumor measurements to assess response and progression, both in routine care and as the primary objective of clinical trials. However, the variability of computed tomography (CT) –based tumor measurement has not been comprehensively evaluated. In this study, we assess the variability of lung tumor measurement using repeat CT scans performed within 15 minutes of each other and discuss the implications of this variability in a clinical context.

Patients and Methods:

Patients with non–small-cell lung cancer and a target lung lesion ≥ 1 cm consented to undergo two CT scans within a period of minutes. Three experienced radiologists measured the diameter of the target lesion on the two scans in a side-by-side fashion, and differences were compared.

Apparent changes in tumor diameter exceeding 1 to 2 mm are common on immediate reimaging. Increases and decreases less than 10% can be a result of the inherent variability of reimaging. Caution should be exercised in interpreting the significance of small changes in lesion size in the care of individual patients and in the interpretation of clinical trial results.

The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer.

Methods:

From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009.

Results:

The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02).

Conclusions:

Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.)

[url]http://www.nejm.org/doi/full/10.1056/NEJMoa1102873

An editorial by Dartmouth's Dr. Hal Sox, that reads in part:

"Individual patients at high risk for lung cancer who seek low-dose CT screening and their primary care physicians should inform themselves fully, and current smokers should also receive redoubled assistance in their attempts to quit smoking. They should know the number of patients needed to screen to avoid one lung-cancer death, the limited amount of information that can be gained from one screening test, the potential for overdiagnosis and other harms, and the reduction in the risk of lung cancer after smoking cessation. The NLST investigators report newly proven benefits to balance against harms and costs, so that physicians and patients can now have much better information than before on which to base their discussions about lung-cancer screening.

The findings of the NLST regarding lung-cancer mortality signal the beginning of the end of one era of research on lung-cancer screening and the start of another. The focus will shift to informing the difficult patient-centered and policy decisions that are yet to come."

99.5% saw no benefit
0.5% were helped by preventing death
23% were harmed by false positive (cancer scare)
3.5% were harmed by undergoing a surgical procedure
0.6% were harmed by suffering a complication of surgery

Narrative: Lung cancer remains the most common cause of cancer death in the US, and smoking remains the most powerful risk factor for lung cancer.1 Early detection offers the potential of treating cancers at an earlier stage and may help to reduce deaths from the disease. The National Lung Screening Trial (NLST) was undertaken to determine whether yearly screening with computed tomography would save lives compared to screening with plain chest radiography. Participants were at very high risk of lung cancer: 55-74 years old with a history of at least 30 pack-years of smoking.

NLST randomized 53,454 to receive annual chest x-rays or CT scans. After 6.5 years the investigators reported a mortality reduction of 0.46% in the group that received CT scans. This number suggests that one life was saved for every 217 people undergoing annual CT when compared to those undergoing annual x-ray.

There were also harms associated with CT lung screening. Compared to x-rays one in 4 people experienced an additional false positive result, one in 29 underwent an unnecessary surgical procedure, and one in 161 had a surgical complication.

Caveats: Early detection has been successful in reducing deaths from cervical cancer, but unsuccessful in reducing deaths from prostate and breast cancers. These failures of early detection may be due in part to ‘overdiagnosis’, in which cancers that would never have posed a threat are unnecessarily treated, with serious consequences.2 As an editorialist points out3 this problem is clearly present in the NLST trial, where CT scanning led to more cancer diagnoses than plain x-ray. In other words, if all detected cancers were aggressive and dangerous then after 6.5 years the major difference between groups should be how cancers were found—not how many there are.

Moreover, in this study CT scans were compared to annual chest x-ray, a screening tool for which studies of a quarter million smokers have already shown no benefit.4,5 In fact, in these studies more chest x-ray screening led to more deaths from lung cancer.5 Comparing a group that undergoes no screening to a group that undergoes CT screening would therefore be a more appropriate, and more realistic, indicator of the many impacts of CT screening. Finally, the surgeries, procedures, surgical complications, and the overwhelming number of false positives caused by CT screening are major down sides and would have to be as carefully communicated as any potential benefits to anyone considering using this modality.

Despite these caveats the significant and surprisingly large reduction in mortality using CT screening in this trial is promising. Because this is the first high quality randomized trial of CT screening it will take multiple further trials to confirm the benefit, and it will be critical to apply these data only to people at very high risk unless future trials expand to include others.

Author: David H. Newman, MD

When I went to my IGoogle homepage today I noticed a story on yet another lung cancer screening article. The story, in Oncology Nurse Advisor but from the HealthDay news service, has a rather provocative headline, “Insurers should screen older smokers for lung cancer”. The story reviewed a recently published study in Health Affairs that is likely to ignite the debate over routine screening for lung cancer yet again. Here are the conclusions from the authors of this well constructed Health Affairs study using actuarial data:

“Our results suggest that commercial insurers should consider lung cancer screening of high-risk individuals to be high-value coverage and provide it as a benefit to people who are at least fifty years old and have a smoking history of thirty pack-years or more. We also believe that payers and patients should demand screening from high-quality, low-cost providers, thus helping set an example of efficient system innovation.”

The authors provide some interesting numbers to back up their conclusion. Of the 18 million or so smokers who fall into their eligibility criteria, they showed a potential for an additional 130,000 additional survivors of lung cancer due to early detection. It’s hard to argue that saving this many lives is not important. But the study does not look into the negative aspects of the double edged sword that is lung cancer screening. While we are constantly berated for being anti-screening, it is important for people to understand what the risks and benefits are for any medical procedure including screenings.

The National Cancer Institute (NCI) previously funded a large study to determine whether screening with low-dose CT, as compared with chest radiography, would reduce mortality from lung cancer among high-risk smokers. The results of the earlier study were published in August 2011 and generated a good deal of discussion in the media. The NCI sponsored study was done in a somewhat different group of long term smokers but there are sufficient similarities for the data to be useful here. The positive rate related to spiral CT scans was 24.2% or about one out of every four people scanned had a positive finding. That would amount to 4,320,000 positive findings if extrapolated to the 18 million smokers discussed in the actuarial study. But 94.6% of these positive results were false positives. That means that 4,086,720 people screened would have a false positive result. All would likely suffer from some degree of angst. Of those with false positive findings, 0.06% had a major complication possibly related to subsequent invasive procedures in the NCI sponsored study. That amounts to 108,000 people who would have a serious adverse event related to a procedure due to a false positive test result. Those events need to be considered when thinking about the 130,000 potential lives saved through screening.

Few medical procedures are without risk and each should be viewed as a double edged sword. Benefits as well as risks need to be considered. Reporting on just the benefits provides readers with only half the story.

Selecting people for lung cancer screening using a modified model based on the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial proved more efficient and sensitive than using criteria from the National Lung Screening Trial (NLST), researchers reported this week.

Use of the modified PLCO model to select appropriate candidates for lung screening programs "could potentially be an effective method leading to improved cost-effectiveness of screening with additional deaths from lung cancer prevented," they conclude.

For institutions planning on implementing a lung cancer screening program for high risk individuals, "using elevated risk as predicted by a proven lung cancer risk prediction model is the method of choice for selecting candidates for screening, compared to using the NLST smoking criteria," Dr. Martin C. Tammemagi an epidemiologist at Brock University, St. Catherines, Ontario, Canada, wrote in an email to Reuters Health.

The NLST published in 2011 showed that lung-cancer screening with the use of low-dose computed tomography (CT) resulted in a 20% reduction in mortality from lung cancer.

Many organizations that now screen for lung cancer use NLST criteria, which include an age between 55 and 74 years, a history of smoking of at least 30 pack-years, a period of less than 15 years since cessation of smoking, or some variant of these criteria. These selection criteria are intended to increase the yield of lung cancers, but they exclude many known risk factors for lung cancer, Dr. Tammemagi and colleagues say.

"Use of an accurate model that incorporates additional risk factors to select persons for screening may identify more persons who have lung cancer or in whom lung cancer will develop, they add.

They previously developed and validated a lung cancer risk-prediction model based on data from former and current smokers in the PLCO cancer screening trial.

Predictors in the PLCO model include age, level of education, body-mass index (BMI), family history of lung cancer, chronic obstructive pulmonary disease (COPD), chest radiography in the previous three years, smoking status (current smoker vs. former smoker), history of cigarette smoking in pack-years, duration of smoking, and quit time.

In the PLCO model, risks are based on a median follow-up of 9.2 years, which exceeds the six-year follow-up in the NLST, making a comparison difficult.

As reported online February 20 in the New England Journal of Medicine, Dr. Tammemagi and colleagues modified and updated the PLCO model to make it directly applicable to NLST data.

Their analyses included 73,618 smokers in the PLCO study and 51,033 NLST participants.

For the modified PLCO model, the area under the curve (AUC) was 0.803 in the development data set and 0.797 in the validation data set. An AUC in this range "may be of value in providing individual-level information and in population-level screening programs," the researchers say.

Overall, the modified PLCO model identified 81 more of the 678 lung cancers (11.9%) than did the NLST criteria (41.3% fewer lung cancers were missed).

Dr. Tammemagi told Reuters Health he's already been approached by several groups who plan to implement the model for enrolling individuals into lung screening programs or research studies. "With application of the prediction model and suitable follow-up we should develop a sense of how well it works in a few years," he said.

Dr. Tammemagi also told Reuters Health, "Currently, the Pan-Canadian Early Detection of Lung Cancer Study has enrolled individuals on the bases of elevated risk according to a prototype of the current lung cancer risk prediction model. In that study 113 cancers have been detected in 2537 enrollees in an average of three years of follow-up. This 4.5% yield of lung cancers is much higher than observed in the National Lung Screening Trial and is very close to that predicted by the model. The Canadian study corroborates the findings we reported in the NEJM article. We expect to publish Canadian study findings shortly."

Lung Cancer. It is a disease that is a deadly, silent killer mainly because it is misunderstood.

Everywhere you look in the month of October you will see pink ribbons and national callout campaigns to help breast cancer research, (i.e., the National Football League).

However, once lung cancer awareness month (November) rolls around, it all seems to slow down again. Lung cancer finds itself asking, “Where are the white ribbons and towels?”

Seemingly, lung cancer can often be overlooked because of the unfair and misunderstood stigma associated with it. People tend to be less sympathetic, because of the assumption that if you have lung cancer, you probably brought it on yourself. Many people feel that lung cancer is a “smoker’s disease,” and while smoking does contribute to lung cancer deaths, a person can get lung cancer from exposure to second-hand smoke, air pollution, radon, asbestos and other occupational hazards.

According to the National Cancer Institute, nearly 160,000 people will pass away from lung cancer in 2013, making lung cancer the cause of more deaths than colon, breast and prostate cancers combined. And yet, less than $1,500 per death will be committed to lung cancer research compared to the more than $20,000 per death for breast cancer.

This fact is not widely known because lung cancer doesn’t get the resources or world-wide exposure, like other cancers. The inequality in funding has kept the five-year survival rate for lung cancer at 15% over the past 40 years while the rate for breast cancer and prostate cancer survival has reached nearly 90%.

This inequality of funding is one of the contributing factors in lung cancer not being diagnosed at an earlier stage.

Each year, more than 219,000 new lung cancer cases are diagnosed, but sadly only 16% (35,040 cases) of lung cancers are diagnosed at an early, more manageable stage — making many diagnoses harder to cure. More funding could help researchers develop tools needed to diagnose patients sooner.

Long Beach Memorial Medical Center has developed an Early Lung Cancer Detection Program, where a 320 CT scan is issued rather than a chest x-ray — allowing images of the lungs to be 100 times more accurate at finding lung cancer than a chest x-ray — giving doctors the ability to detect lung cancer at earlier stages, before it is too late.

Long Beach Memorial knows that more needs to be done to increase lung cancer survivorship and raise awareness. For every one person who is aware, and for every additional dollar raised, the Long Beach community can combat this deadly disease.

The MemorialCare Todd Cancer Institute (TCI) at Long Beach Memorial is helping to “clear the air” about lung cancer, and hosted Long Beach’s “Shine a Light on Lung Cancer” event at 4 p.m. Sunday, Nov. 3, at the Todd Cancer Pavilion. The event helped raise awareness and provide a voice for millions impacted by lung cancer, including lung cancer survivors and those who are remembering loved ones.

Dr. Robert Nagourney is an oncologist at MemorialCare’s Todd Cancer Institute at Long Beach Memorial Medical Center.